tbuckley/cabot-search huggingface dataset:
Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry
Authors: Long Liu, Xingxing Yu, Zhifeng Li, Xiaohua He, Jie Zha, Zhijuan Lin, Yan Hong, Huijian Zheng, Qian Lai, Kaiyang Ding, Xian Jia, Guo Fu, Haifeng Yu, Haiyan Yang, Zhiming Li, Ken H. Young, Bing Xu
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Patients with follicular lymphoma (FL) who experience disease progression within 24 months (POD24) have inferior outcomes. The tumor immune microenvironment (TIME) plays a crucial role in pathogenesis and progression of follicular lymphoma (FL). However, TIME evolution during progression of disease within 24 months (POD24) is elusive. Methods Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively analyze the TIME structure in 13 paired FLs at diagnosis and POD24. Results Follicles and peri-follicular regions were well dissected in structure. Peri-follicular regions represented a barrier for immune infiltration into the follicles. More FL-cells in the peri-follicular regions suffered CD8 + T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163 − macrophages with PD-1 ligand upregulation and decreased CD8 + T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles. Spatial analyses demonstrated that FL-cells interacted more intimately with macrophages than with Tregs and less with cytotoxic T cells in both peri-follicular regions and follicles during POD24. In comparison, macrophages also cooperated more frequently with Tregs to simultaneously hijack FL-cells, creating an enhanced immunosuppressive environment in both peri-follicular and follicular regions during POD24. Conclusions Peri-follicular regions function as a barrier by recruiting both CD8 + T cells and immunosuppressive cells, protecting follicular FL-cells from immune attack at diagnosis or POD24. FL-cells reside in a more immune-compromised microenvironment and evade immune cell attacks during POD24. Novel immunotherapeutic approaches harnessing LAG-3, macrophages, and Tregs will be empowered to overcome poor outcomes in patients with FL POD24.
Cardiorenal Outcomes With Ertugliflozin by Baseline Metformin Use: Post Hoc Analyses of the VERTIS CV Trial
Authors: Francesco Cosentino, Christopher P. Cannon, Robert Frederich, David Z.I. Cherney, Samuel Dagogo-Jack, Richard E. Pratley, James P. Mancuso, Mario Maldonado, Nilo B. Cater, Shuai Wang, Darren K. McGuire
Journal: Circulation (2022)
Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank
Authors: Jordana B. Cohen, Gary F. Mitchell, Dipender Gill, Stephen Burgess, Mahboob Rahman, Thomas C. Hanff, Vasan S. Ramachandran, Karen M. Mutalik, Raymond R. Townsend, Julio A. Chirinos
Journal: Circulation Research (2022)

Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses.
Resident Assessment—What Is Our Mission?
Authors: Ian M. Kratzke, Muneera R. Kapadia
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Expanding Options for Total Intravenous Anesthesia—The Etomidate vs Propofol for In-Hospital Complications Trial
Authors: Jason M. Johanning
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Dupilumab Drug Survival and Associated Predictors in Patients With Moderate to Severe Atopic Dermatitis
Authors: Lotte S. Spekhorst, Marlies de Graaf, Nicolaas P. A. Zuithoff, Juul M. P. A. van den Reek, Marijke Kamsteeg, Celeste M. Boesjes, Geertruida L. E. Romeijn, Laura Loman, Inge Haeck, Albert J. Oosting, Astrid de Boer-Brand, Wouter R. H. Touwslager, Annebeth Flinterman, Anneke M. T. van Lynden-van Nes, Antoni H. Gostynski, Marjolein S. de Bruin-Weller, Marie-Louise Schuttelaar
Journal: JAMA Dermatology (2022)

Long-term data on dupilumab drug survival in patients with atopic dermatitis (AD) are scarce. Furthermore, little is known about the factors associated with drug survival of dupilumab in AD.To describe the drug survival of dupilumab in patients with AD and to identify associated predictors.This cohort study was based on data from the multicenter prospective daily practice BioDay registry, in which 4 university and 10 nonuniversity hospitals in the Netherlands participated. Analysis included patients (age ≥18 years) participating in the BioDay registry with a follow-up of at least 4 weeks. The first patient treated with dupilumab was recorded in the BioDay registry in October 2017; data lock took place in December 2020, and data analysis was performed from October 2017 to December 2020.Drug survival was analyzed by Kaplan-Meier survival curves and associated characteristics by using univariate and multivariate Cox regression analysis.A total of 715 adult patients with AD (mean [SD] age, 41.8 [16.0] years; 418 [58.5%] were male) were included with a 1-year, 2-year, and 3-year overall dupilumab drug survival of 90.3%, 85.9%, and 78.6%, respectively. Characteristics associated with shorter drug survival owing to ineffectiveness were the use of immunosuppressant drugs at baseline (hazard ratio [HR], 2.64; 95% CI, 1.10-6.37) and being a nonresponder at 4 weeks (HR, 8.68; 95% CI, 2.97-25.35). Characteristics associated with shorter drug survival owing to adverse effects were the use of immunosuppressant drugs at baseline (HR, 2.69; 95% CI, 1.32-5.48), age 65 years or older (HR, 2.94; 95% CI, 1.10-7.87), and Investigator Global Assessment score of very severe AD (HR, 3.51; 95% CI, 1.20-10.28).This cohort study demonstrated a good overall 1-year, 2-year, and 3-year dupilumab drug survival. Patients using immunosuppressive therapy at baseline and those with an absence of treatment effect at week 4 tended to discontinue treatment owing to ineffectiveness more frequently. Using immunosuppressant drugs at baseline, older age, and Investigator Global Assessment score of very severe AD were characteristics associated with an increased risk for discontinuation owing to adverse effects. These data provide more insight and new perspectives regarding dupilumab treatment in AD and can contribute to the optimization of patient outcomes.
Annals Graphic Medicine - Trach and Peg
Authors: Paloma C. Orozco Scott
Journal: Annals of Internal Medicine (2022)

Web ExclusivesSeptember 2022Annals Graphic Medicine - Trach and PegFREEPaloma C. Orozco Scott, MAPaloma C. Orozco Scott, MAIcahn School of Medicine at Mount Sinai, New York, New York (P.C.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0012 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Icahn School of Medicine at Mount Sinai, New York, New York (P.C.S.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0012.Author/Illustrator Information: Paloma C. Orozco Scott, MA, is a fourth-year medical student at the Icahn School of Medicine at Mount Sinai. To see more of their work, visit https://brown.digication.com/paloma-orozco-scott (e-mail, pc.[email protected]com).This article was published at Annals.org on 23 August 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics September 2022Volume 175, Issue 9Page: W112-W113 ePublished: 23 August 2022 Issue Published: September 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France
Authors: Jérémie Botton, Marie Joelle Jabagi, Marion Bertrand, Bérangère Baricault, Jérôme Drouin, Stéphane Le Vu, Alain Weill, Paddy Farrington, Mahmoud Zureik, Rosemary Dray-Spira
Journal: Annals of Internal Medicine (2022)

The BNT162b2 (Pfizer-BioNTech) vaccine has been shown to be safe with regard to risk for severe cardiovascular events (such as myocardial infarction [MI], pulmonary embolism [PE], and stroke) in persons aged 75 years or older. Less is known about the safety of other COVID-19 vaccines or outcomes in younger populations.To assess short-term risk for severe cardiovascular events (excluding myocarditis and pericarditis) after COVID-19 vaccination in France's 46.5 million adults younger than 75 years.Self-controlled case series method adapted to event-dependent exposure and high event-related mortality.France, 27 December 2020 to 20 July 2021.All adults younger than 75 years hospitalized for PE, acute MI, hemorrhagic stroke, or ischemic stroke (n = 73 325 total events).Linkage between the French National Health Data System and COVID-19 vaccine databases enabled identification of hospitalizations for cardiovascular events (MI, PE, or stroke) and receipt of a first or second dose of the Pfizer-BioNTech, mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine. The relative incidence (RI) of each cardiovascular event was estimated in the 3 weeks after vaccination compared with other periods, with adjustment for temporality (7-day periods).No association was found between the Pfizer-BioNTech or Moderna vaccine and severe cardiovascular events. The first dose of the Oxford-AstraZeneca vaccine was associated with acute MI and PE in the second week after vaccination (RI, 1.29 [95% CI, 1.11 to 1.51] and 1.41 [CI, 1.13 to 1.75], respectively). An association with MI in the second week after a single dose of the Janssen vaccine could not be ruled out (RI, 1.75 [CI, 1.16 to 2.62]).It was not possible to ascertain the relative timing of injection and cardiovascular events on the day of vaccination. Outpatient deaths related to cardiovascular events were not included.In persons aged 18 to 74 years, adenoviral-based vaccines may be associated with increased incidence of MI and PE. No association between mRNA-based vaccines and the cardiovascular events studied was observed.None.
Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial
Authors: Antonio Fagundes, David A. Morrow, Kazuma Oyama, Remo H.M. Furtado, Thomas A. Zelniker, Minao Tang, Julia F. Kuder, Sabina A. Murphy, Andrew Hamer, Anthony C. Keech, Peter Sever, Robert P. Giugliano, Marc S. Sabatine, Brian A. Bergmark
Journal: Journal of the American College of Cardiology (2022)
Sequential oxygen supply system promotes peripheral nerve regeneration by enhancing Schwann cells survival and angiogenesis
Authors: Teng Ma, Yiming Hao, Shengyou Li, Bing Xia, Xue Gao, Yi Zheng, Liangwei Mei, Yitao Wei, Changbin Yang, Lei Lu, Zhuojing Luo, Jinghui Huang
Journal: Biomaterials (2022)
Polygenic Risk Score Predicts Sudden Death in Patients With Coronary Disease and Preserved Systolic Function
Authors: Roopinder K Sandhu, Jacqueline S Dron, Yunxian Liu, M Vinayaga Moorthy, Neal A Chatterjee, Patrick T Ellinor, Daniel I Chasman, Nancy R Cook, Amit V Khera, Christine M Albert
Journal: Journal of the American College of Cardiology (2022)
Impact and Modifiers of Ventricular Pacing in Patients With Single Ventricle Circulation
Authors: Henry Chubb, Anica Bulic, Douglas Mah, Jeremy P Moore, Jan Janousek, Jennifer Fumanelli, S Yukiko Asaki, Andreas Pflaumer, Allison C Hill, Carolina Escudero, Sit Yee Kwok, Jasveer Mangat, Luis A Ochoa Nunez, Seshadri Balaji, Eric Rosenthal, William Regan, Michaela Horndasch, Hiroko Asakai, Ronn Tanel, Richard J Czosek, Ming-Lon Young, David J Bradley, Thomas Paul, Peter Fischbach, Lindsey Malloy-Walton, Doff B McElhinney, Anne M Dubin
Journal: Journal of the American College of Cardiology (2022)
Comparative Risks of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease
Authors: Ellen S. Regalado, Shaine A. Morris, Alan C. Braverman, Ellen M. Hostetler, Julie De Backer, Ruosha Li, Reed E. Pyeritz, Anji T. Yetman, Elena Cervi, Sherene Shalhub, Richmond Jeremy, Scott LeMaire, Maral Ouzounian, Arturo Evangelista, Catherine Boileau, Guillaume Jondeau, Dianna M. Milewicz
Journal: Journal of the American College of Cardiology (2022)

Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes. This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene. A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, and location of recruitment. Significant differences in aortic event risk were identified among the smooth muscle contraction genes (ACTA2, MYLK, and PRKG1; P = 0.002) and among the genes for Loeys-Dietz syndrome, which encode proteins in the transforming growth factor (TGF)-β pathway (SMAD3, TGFB2, TGFBR1, and TGFBR2; P < 0.0001). Cumulative incidence of type A aortic dissection was higher than elective aneurysm surgery in patients with variants in ACTA2, MYLK, PRKG1, and SMAD3; in contrast, patients with TGFBR2 variants had lower cumulative incidence of type A aortic dissection than elective aneurysm surgery. Cumulative incidence of type B aortic dissection was higher for ACTA2, PRKG1, and TGFBR2 than other genes. After adjusting for proband status, sex, and recruitment location, specific variants in ACTA2 and TGFBR2 were associated with substantially higher risk of aortic event with childhood onset. Gene- and variant-specific data on aortic events in individuals with HTAD support personalized aortic surveillance and clinical management.
National-level overall survival patterns for molecularly-defined diffuse glioma types in the United States
Authors: Quinn T Ostrom, Madison L Shoaf, Gino Cioffi, Kristin Waite, Carol Kruchko, Patrick Y Wen, Daniel J Brat, Jill S Barnholtz-Sloan, J Bryan Iorgulescu
Journal: Neuro-Oncology (2022)

Molecularly-defined diffuse glioma types-including IDH-wildtype glioblastoma, IDH-mutant astrocytoma, IDH-mutant 1p/19q-codeleted oligodendroglioma, and H3 K27M-mutant diffuse midline glioma-were incorporated into U.S. cancer registry reporting for individuals with brain tumors beginning in 2018. We leveraged these new data to estimate the national-level overall survival (OS) patterns associated with glioma integrated diagnoses.
Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes
Authors: Hiroki Kobayashi, Helen C. Looker, Eiichiro Satake, Francesca D’Addio, Jonathan M. Wilson, Pierre Jean Saulnier, Zaipul I. Md Dom, Kristina O’Neil, Katsuhito Ihara, Bozena Krolewski, Hannah S. Badger, Adriana Petrazzuolo, Domenico Corradi, Andrzej Galecki, Parker C. Wilson, Behzad Najafian, Michael Mauer, Monika A. Niewczas, Alessandro Doria, Benjamin D. Humphreys, Kevin L. Duffin, Paolo Fiorina, Robert G. Nelson, Andrzej S. Krolewski
Journal: Science Translational Medicine (2022)

Circulating proteins associated with transforming growth factor-β (TGF-β) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which of these proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESKD) in humans. Using the SOMAscan proteomic platform, we measured concentrations of 25 TGF-β signaling family proteins in four different cohorts composed in total of 754 Caucasian or Pima Indian individuals with type 1 or type 2 diabetes. Of these 25 circulating proteins, we identified neuroblastoma suppressor of tumorigenicity 1 (NBL1, aliases DAN and DAND1), a small secreted protein known to inhibit members of the bone morphogenic protein family, to be most strongly and independently associated with progression to ESKD during 10-year follow-up in all cohorts. The extent of damage to podocytes and other glomerular structures measured morphometrically in 105 research kidney biopsies correlated strongly with circulating NBL1 concentrations. Also, in vitro exposure to NBL1 induced apoptosis in podocytes. In conclusion, circulating NBL1 may be involved in the disease process underlying progression to ESKD, and its concentration in circulation may identify subjects with diabetes at increased risk of progression to ESKD.
Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function
Authors: Shawn J. Macha, Balakrishna Koneru, Trevor A. Burrow, Charles Zhu, Dzmitry Savitski, Rakhshanda L. Rahman, Catherine A. Ronaghan, Jonas Nance, Kristyn McCoy, Cody Eslinger, C. Patrick Reynolds
Journal: Cancer Research (2022)

A subset of cancers across multiple histologies with predominantly poor outcomes use the alternative lengthening of telomeres (ALT) mechanism to maintain telomere length, which can be identified with robust biomarkers. ALT has been reported to be prevalent in high-risk neuroblastoma and certain sarcomas, and ALT cancers are a major clinical challenge that lack targeted therapeutic approaches. Here, we found ALT in a variety of pediatric and adult cancer histologies, including carcinomas. Patient-derived ALT cancer cell lines from neuroblastomas, sarcomas, and carcinomas were hypersensitive to the p53 reactivator eprenetapopt (APR-246) relative to telomerase-positive (TA+) models. Constitutive telomere damage signaling in ALT cells activated ataxia-telangiectasia mutated (ATM) kinase to phosphorylate p53, which resulted in selective ALT sensitivity to APR-246. Treatment with APR-246 combined with irinotecan achieved complete responses in mice xenografted with ALT neuroblastoma, rhabdomyosarcoma, and breast cancer and delayed tumor growth in ALT colon cancer xenografts, while the combination had limited efficacy in TA+ tumor models. A large number of adult and pediatric cancers present with the ALT phenotype, which confers a uniquely high sensitivity to reactivation of p53. These data support clinical evaluation of a combinatorial approach using APR-246 and irinotecan in ALT patients with cancer.This work demonstrates that constitutive activation of ATM in chemotherapy-refractory ALT cancer cells renders them hypersensitive to reactivation of p53 function by APR-246, indicating a potential strategy to overcome therapeutic resistance.
Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas
Authors: Heike Horn, Vindi Jurinovic, Ellen Leich, Sabrina Kalmbach, Julia Bausinger, Annette M. Staiger, Katrin S. Kurz, Peter Möller, Heinz-Wolfram Bernd, Alfred C. Feller, Karoline Koch, Wolfram Klapper, Harald Stein, Martin-Leo Hansmann, Sylvia Hartmann, Gabriel Scheubeck, Martin Dreyling, Wolfgang Hiddemann, Klaus Herfarth, Marianne Engelhard, Andreas Rosenwald, Eva Hoster, German Ott
Journal: HemaSphere (2022)

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as BCL2 translocations to determine their impact on clinical outcome of LFL patients. The frequency of chromosomal deletions in 1p and 17p was comparable between LFL and SFL, while 6q deletions and BCL2 translocations more frequently occurred in SFL. A higher proportion of 1p deletions was seen in BCL2 -translocation–positive LFL, compared with BCL2 -translocation–negative LFL. Deletions in chromosomes 1p, 6q, and 17p predicted clinical outcome of patients with SFL in the entire cohort, while only deletions in chromosome 1p retained its negative prognostic impact in R-CHOP–treated SFL. In contrast, no deletions in one of the investigated genetic loci predicted clinical outcome in LFL. Likewise, the presence or absence of BCL2 translocations had no prognostic impact in LFL. Despite representing a genetic portfolio closely resembling SFL, LFL showed some differences in deletion frequencies. BCL2 translocation and 6q deletion frequency differs between LFL and SFL and might contribute to distinct genetic profiles in LFL and SFL.